Coffeinum

Volume II — Main text

Caffeinum, an alkaloid obtained from coffee, C8H10N4O2. I. Provings.-1 . C. G. LEHMANN took to gr. and felt nothing. The urine only contained more urea. He gave it to many of his pupils in doses of from 2 to 10 gr. The urine contained more urea. There occurred the most violent excitation of vascular and nervous systems, palpitation, very rapid, irregular, often intermittent pulse, oppression of chest, headache, obscuration of senses, tinnitus aurium, vision of sparks, sleeplessness, erections, and even delirium. Five who had taken from 5 to 10gr. were unfit for work next d. (BRILL, Das Kaffein, 79.) 2. FRERICHS took 25 gr. at once. After h . pulse was full and hard, rose from 70 to 80, head heavy and confused, roaring in ears, and slight vertigo, pulsation of temporal arteries very visible.* Great restlessness and excitement, unable to continue one train of thought. * Husemann, after 0.24 grm., experienced intense congestion of head and diffi-. culty ofbreathing (LEWIN, op. cit.).

After I h. vomiting with cessation of symptoms. ( Handwörterb. der Physiologie, iii, 721.) 3. In J. LEHMANN's experiments with coffee and caffeinum the urea was occasionally diminished in quantity ; 8 gr. caused rapid pulse, strong heart's action, trembling, constant urging to urinate with scanty discharge, excitement of imagination, confusion of thoughts, visions, a sort of intoxication, and, lastly, profound sleep. (BRILL, op. cit., 83.) 4. Dr. EUSTRATIADES found that caffein diminished the quantity of urea in the doses of 15 centigr. daily by It per cent.; in doses of 30 centigr. daily, by 28 per cent. He found that strong coffee (roasted) in infusion had the same effect. He also notes that caffeine is not diuretic, though it causes more frequent desire to micturate ; that his pulse, ordinarily 70-75, fell (while taking 30 centigr. daily) to 58- 65, and was more regular and tranquil ; that little effect was produced on sleep, save for a n. or two after commencing larger dose. The effects of coffee were very similar. (Etude sur les propriétés phys. de la Caféine et du Café, Paris, 1870.) II. Poisonings.- 1 . A woman took two powders of the citrate, each containing 0.24 grm. She was seized with remarkable restlessness and dizziness, and could not keep erect ; violent præcordial anxiety with palpitation ; abdominal pulsation ; violent trembling of all extremities ; grating of teeth ; features expressive of utmost anxiety ; feeling of constriction of neck and throat, recurring every 15 m.; pulse very rapid. This condition lasted 3 h., and gradually disappeared. (KELP, in Schmidt's Jahrb., vol. 176, p. 220.) 2. Man, æt. 63, in good health, took by mistake on Feb. 20th, 1883, 3j of citrate. There followed immediately burning in throat and gullet, followed by giddiness, faintness, nausea, numbness, and tremors of extremities ; pain and tenderness of bowels and stomach ; great thirst ; dry tongue. At 4.45 he was violently sick and purged. Much urine was also passed. Sickness and vomiting recurred at 5.45. On leaving closet he could hardly walk and had to be assisted. At 6 he was collapsed ; pulse hardly perceptible, irregular, 120 ; skin cold and clammy, but all senses perfectly intact, not even headache ; sensibility of skin nowhere impaired, a symptom not presented throughout. [Antidotes were now given, including nitrite of amyl and nitroglycerine, and collapse gradually passed off. As it did so, lumbar pain and tenderness came on, and continued in some degree till 24th.] (Routh, Lancet, April 21st, 1883.) III. Experiments on animals.-I. AUBERT experimented principally on frogs and dogs. His experiments were made with the alkaloid obtained from yellow Java coffee. a. Nervous System. The prominent effect of C. is an increased irritability of reflex nervous action and tetanus. The symptoms are somewhat similar to those of strychnia, i. e. sudden starting upon touching the animal, or after exposing it to the slightest concussion, increased irritation producing tetanic spasms. The larger the dose of C. the longer do the latter last. That these reflex motions are produced through the excito-motor nerves (spinal cord) and not by acting directly on the contractility of the muscular fibres, was proven by

artificial isolation of the nerves from the muscles of one leg (dividing the sciatic nerve), when no contractions took place in that limb ; while, when said nerve was left intact, but dissected out from between the muscles and the latter constricted by tying a string around them (not including the nerve) even to the extent of compressing the bloodvessels, reflex contractions occurred. Besides the increased irritability of spinal nerves, it was found that the sympathetic nerve lost, to some extent, its activity, for all the smaller blood-vessels became relaxed, and passive congestion occurred, which produced upon muscles separated from spinal nerve influence at first slight contractions and subsequent relaxations . b. Respiration.-The only but very interesting result ofexperiments in this direction was the elicitation of the fact that respiration was more or less suppressed during the tetanic spasms, but also that the spasms ceased when artificial respiration was resorted to. c. Heart and Circulation. In this direction the following results were obtained : (a) Increase of frequency of the beat of the heart, and therefore of the pulse ; (6) the sphygmograph showed that the pulsewave was lower ; (c) the pressure of the column of blood was diminished ; (d) the cavities of the heart emptied themselves only partly ; (e) chloral antidotes the symptoms of the heart. (Pflüger's Archiv, v, 589.) 2. From 4 to 7 gr. acted on rabbits. In the first h. the irritability was increased and went on increasing shown by greater attention to trivial irritations, timidity, starting at sounds, and great motility. Heart's beats increased in frequency (from 160 to 240) ; this remained for hours or even days ; respirations not increased by small doses, sank from 60 to 40-32 from large doses. Temperature slightly increased, pupils unaltered. Involuntary muscles increased in activity, passed dung and urine oftener, urine increased in quantity. The increased motility of voluntary muscles after large doses decreased. Death was preceded by tetanic convulsions. (KURZAK, Zeitsch. d. Ges. d. Aerzt., zu Wien, 1860, No. 40.) 3. The following is a summary of results obtained by hypodermic injection of caffeine. 1 a. In frogs, after gr. g, very slight weakness of posterior extre- 1 mities ; after gr. 3 , considerable weakness of limbs, respiration 1 impaired, reflex action diminished ; after gr. To, almost complete paralysis and loss of reflex action, respiration stopped, prostration, cutaneous surface congested ; after gr. 1, complete prostration, reflex action lost, respiration stopped, under surface of skin, tongue and mouth congested, stasis of blood in capillaries. From gr. and symptoms still more intense. Death followed doses from upwards ; post mortem, heart beat feebly, great congestion of viscera, when brain, cord, nerves or muscles were irritated muscular contractions followed. In frogs which had , on touching all columns of exposed cord during life muscular contractions ; but after injection touching posterior columns had no such effect. In two frogs which had gr. to 1 femoral artery was ligatured ; but no difference was perceived between two limbs . b. A rabbit had 4 doses of gr.jeach. After Ist and 2nd, no effects ;

after 3rd, congestion of ears, cerebral excitement, contraction ofpupil, staggering gait ; from 4th, partial paralysis of limbs and diminished reflex action . c. Another had 4 gr. at once. Respirations and pulsations, at first increased, then diminished ; ears at first anæmic and cold, then congested and hot; breathing laboured ; pupils contracted ; paralysis of limbs ; loss of reflex action ; tetanic (opisthotonic) spasms. P.M. -Membranes ofbrain and internal viscera congested ; substance of brain and cord healthy ; galvanism of brain, cord, nerves or muscles produced muscular contractions. d. Three cats had doses of6-8 gr. Former produced irritation and cerebral excitement ; congestion oftongue and mouth ; staggering gait ; tenesmus and mucous discharge from bowel ; excessive salivation ; subsequent depression. In 2nd (8 gr. ) same, with prostration, loss of reflex action, tetanic spasms, and death. In 3rd no marked effect for about h., then death from sudden tetanic spasm. Same p.m. appearances as before. e. A rabbit had 12 gr. Spinal eord being exposed during life, and posterior columns touched with needle, animal struggled and cried out ; anterior columns touched, it struggled only. After injection, when posterior columns were touched, animal did not cry out, but struggled slightly ; anterior columns touched, strong muscular contractions ensued. Symptoms as before. (Hughes Bennett, Antagonism of Medicines, 1873, p. 73.)

Volume IV — Appendix

CAFFEINUM.

(See vol. ii, p. 313.)

II. 3. A single woman of 30, being exceedingly nervous from loss of sleep and somewhat immoderate use of stimulants, was advised to take a a gr. powder of citrate of C. By mistake she took 3 gr., and impatiently repeated the dose several times, so that within i) h. she had taken 18 gr. (She took also — getting no relief — a ^ gr. morphia pill before she began to feel the effects of the C. ; but it does not seem to have played any material part in the phenomena that ensued.) She passed a restless, wakeful, and almost delirious n. Respiration and heart's action were hurried and irregular. Reflex excitability was marked for a time, when general muscular weakness supetvttA^ \ «sA.

towards m. she fell into a state of stupor, in] Extremities were cold ; there was clamnv and slight paresis of muscles of hands and fj pulse 55, and somewhat irregular ; resp. I pupils but slightly contracted, responding n persistent contraction of flexor muscles of fi of extensors, especially of thumbs and grci spasmodic action of muscles of calves, w" termed cramp-like pains. She vomited oci of warmth, with whisJcy by mouth and at dermically, she rallied, recovering conscious) complained of severe paroxysmal pains in al colic i also of dimness of vision, with a time, becoming quite delirious, partly due t out of bed and endeavoured to walk across stand on her feet, reeled like one intoxicat© vertigo, with feeling of numbness in soles j for an attendant close at hand. A certain tf of both hands, with tremors of tongue, excessive, with dryness of mouth and tongi of ice. There was no headache whatever, supra-orbital region. Speech was somewhat at times thick ; and there was also some Heart's action was diminished in rapidity, al Urination was frequent and copious. Ab arrival she complained rather suddenly of sQ extending upwards and gradually implic chest and neck ; when a sudden and severe of marked tetanic character, abdominal am retracted and rigid. Eyes were suffused, a: of great pain ; resp. was entirely checked, with jaws quite rigid, and fingers firmly con by a second convulsive seizure of the same Chloral and k. brom. were now given, whi and from this time forward patient gradu thesia, and the paresis of hands and feel, did the 5th d. {N. K Med, Journ.y Sept. 19,

Volume IV — Supplement

CAFFEINUM.

(See vol. ii, p. 313 ; 'ol. ir, p. 5*5.)

I. 5. Dr. Leblond experimented on himself, injecting drug under •!! of abdomen. He abstained from cofFee during his provings, and " a week before their commencement. Marc/s sphygmograph was

«. Pulse 76—80 (after repose), at 5.45 p.m. 10 centigr. were

«ken. 6.15, pulse 64 ; ascending line of curve straight, descending

'^^ undulating. 6.45, pulse 56 ; a marked plateau at summit of

*^'^C 7, pulse 54 ; same curve, ascending line being quite abrupt.

, *- After 4 h. exercise, pulse 80 — 84. At 6 p.m., took 20 centigr.

*3c>^ pulse 78 ; ascending line very abrupt and high. 7, pulse 72 ;

J **■« tracing. 7.30, pulse 64 ; plateau now apparent. 8, pulse 62,

•*^«nding fine undulating.

<'. After 4 h. quiet, pulse 80, at 3.30 p.m. took 30 centigr. 4,

^V*** 70 » 4-30» 62. 5, pulse 54 ; ascent abrupt, descent presents a

"^"^^^ of undulations. 5.30, pulse 54. 6, pulse 52, filiform ; tracing

'^^^^•anbles that of mitral insufficiency. 6.30, pulse of better quality

'^*" 15 m. exercise, but still only 56. 6,40, pulse again filiform ; it

«>«i«iiiued at 52 till 7.5, when it fell to 50 at 7.10, and 48 at 7.20.

^*'Owaa 8 it began to regain force and frequency, and had become

noraaraal (after dinner) by 9.30.

^^- After 40 centigr., similar results followed. Pulse, 74 — 78 at

^**^* »»»encement, had fallen in 2^ h. to 52. After 3 h. it was 56, but

^^■^y fteble and filiform ; at same time there were frequent fibrillary

5^'**^^'ng» in muscles of arms and legs, which in 15 m. more had

i.^' ''•d also masseters and tongue ; face was pale. Re-action set in

after 3}h. ^ *^

*- Pulse 80, at I p.m. took 50 centigr. 1.30, pulse very weak,

"4- 1.35, sense of emptiness in head and of weight over eyes, objects

•f*™* covered with a thin mist ; pulse 60, slightly irregular, filiform at

times and then again stronger. 2.5, after 5 m. walking about room,

pulse rose a little, but on resting again fell to 56. It beat at same rate

at z.ao, and was very feeble and compressible. It did not begin to

^g»in fulness and force till 7.15, and even then was quite slow ;

during this time there had been coldness and some creeping in lower

extremities j slight vertigo and some tremor on walking ; and a little

pnecordial anxiety. At 7.30 a walk in room raised pulse to 70, but

aner a minute s rest it fell to rg again. After a late dinner pulse went

vom ^ therewith was ''" lassitude, some giddiness, and

,i„-^. * ^'JP^riments wer^ ^«r made with a view of ascertaining ttc changes ii* ^^^ iM-cjs^,^?^'' induced by C. After 04 centigr. it

‘was found increased ; there was also coldness of extremities. After 24 milligr. same increase was noted ; and though pulse fell from 76— 80 to 50, it lost power for a short time only.

The temperature was next observed, A thermometer closely held in 1, hand for } h. marked 35—35"5° (Cent.), while that in mouth was 37°. This was at 3.15, and 24 centigr. of C. were then injected, At 3.35 thermometers were replaced, and after } h. that in hand was 23°5%, the other remaining at 37°. At 5.50 the former was 21°8° only, at which point it continued till 6.10, from which time it gradually ascended till it reached 32°. Pulse had fallen from 74 to 54.

On two other occasions similar results followed 36 cemtigr, peripheric temp. falling in former from 36°6° to 27°8°, in latter from 36°8° to 26°. In both experiments there were fibrillary twitchings, Which in former were so intense in the masseters that there was fear of breaking the thermometer in the mouth. In the second trial sphygmographic tracings were taken every 5 m. Slowing of the heart followed promptly, with at first augmentation but later diminution of the force of its beats ; later still, their energy became renewed.

i. After 2 injections of 24 centigr. each at 3.2 p.m., usual effects followed on pulse and temp. Therewith were in first 2 h. frequent yawnings, somnolence, and incessant desire to stretch the limbs. 5.25, slight dimnes of sight on trying to fx an object tracing showed very short ascent, slightly undulating descent (pulse at this time slow and filiform), §.30, yawnings more frequent ; general lassitude ; nausea ; inability for steady reading. 5.40, nausea increasing. After a minutes walking, trembling in lias, impatience, slight Lachrymation and salivation. 6.15, efforts to vomit, nothing coming up but. viscid and rather bitter matters; weakness of limbs. 6.30, some twitching in calves. 9, vomiting of a portion of dinner taken at 7.30. During 4, impossibility, alike in hand and mind, to play piano. 11, pulse 78, slight headache. N, was quiet.

‘js In another experiment, the peripheric temp, was noted with a thermometer in each hand, and it was found to fall much lower on r. side than on 1, It was also noted that every time a cigarette was smoked while the effects lasted, a fresh fall of temp. occurred, though there was some acceleration of heart's action. (Etude sur la Coféine, Paris, 1883.)